Late-Onset Sepsis among Extremely Preterm Infants of 24-28 Weeks Gestation: An International Comparison in 10 High-Income Countries.

INTRODUCTION: Despite advances in neonatal care, late-onset sepsis remains an important cause of preventable morbidity and mortality. Neonatal late-onset sepsis rates have decreased in some countries, while in others they have not. Our objective was to compare trends in late-onset sepsis rates in 9 population-based networks from 10 countries and to assess the associated mortality within 7 days of late-onset sepsis. METHODS: We performed a retrospective population-based cohort study. Infants born at 24-28 weeks' gestation between 2007 and 2019 were eligible for inclusion. Late-onset sepsis was defined as a positive blood or cerebrospinal fluid culture. Late-onset sepsis rates were calculated for 3 epochs (2007-11, 2012-15, and 2016-19). Adjusted risk ratios (aRRs) for late-onset sepsis were calculated for each network. RESULTS: Of a total of 82,850 infants, 16,914 (20.4%) had late-onset sepsis, with Japan having the lowest rate (7.1%) and Spain the highest (44.6%). Late-onset sepsis rates decreased in most networks and remained unchanged in a few. Israel, Sweden, and Finland showed the largest decrease in late-onset sepsis rates. The aRRs for late-onset sepsis showed wide variations between networks. The rate of mortality temporally related to late-onset sepsis was 10.9%. The adjusted mean length of stay for infants with late-onset sepsis was increased by 5-18 days compared to infants with no late-onset sepsis. CONCLUSIONS: One in 5 neonates of 24-28 weeks' gestation develops late-onset sepsis. Wide variability in late-onset sepsis rates exists between networks with most networks exhibiting improvement. Late-onset sepsis was associated with increased mortality and length of stay.

Close Collaboration with Parents Affects the Length of Stay and Growth in Preterm Infants: A Register-Based Study in Finland.

INTRODUCTION: This study aimed to evaluate how Close Collaboration with Parents (CC), a neonatal intensive care unit (NICU)-wide educational model for healthcare staff to improve their family-centred care practices, affects the length of stay (LOS), growth, and later hospital visits and rehospitalizations of preterm infants. METHODS: This register-based study included all preterm infants born below 35 weeks of gestation in Finland from 2006 to 2020. Eligible infants were classified into the Full Close Collaboration (Full-CC) group (n = 2,104) if the NICUs of both the delivery and discharge hospitals had implemented the intervention; into the Partial-CC group (n = 515) if only one of the NICUs had implemented the intervention; and into the control group (n = 11,621) if neither had implemented the intervention. RESULTS: The adjusted LOS, the primary outcome, was 1.8 days or 6% shorter in the Full-CC group than in the control group (geometric mean ratio 0.94, 95% confidence interval [95% CI] 0.89-1.00). Growth was better in the Full-CC group compared to the control group: adjusted group difference 11.7 g/week (95% CI, 1.4-22.0) for weight, 1.3 mm/week (95% CI, 0.6-2.0) for length. The Full-CC group infants had lower odds of having any unscheduled outpatient visits compared to the control group (adjusted odds ratio 0.81; 95% CI, 0.67-0.98). No significant differences were found in any other comparisons. DISCUSSION/CONCLUSION: The unit-wide intervention improving family-centred care practices in NICUs may lead to more efficient use of hospital resources by shortening the LOS, improving growth, and decreasing hospital visits of preterm infants.

Trends, Characteristic, and Outcomes of Preterm Infants Who Received Postnatal Corticosteroid: A Cohort Study from 7 High-Income Countries.

INTRODUCTION: Our objective was to evaluate the temporal trend of systemic postnatal steroid (PNS) receipt in infants of 24-28 weeks' gestational age, identify characteristics associated with PNS receipt, and correlate PNS receipt with the incidence of bronchopulmonary dysplasia (BPD) and BPD/death from an international cohort included in the iNeo network. METHODS: We conducted a retrospective study using data from 2010 to 2018 from seven international networks participating in iNeo (Canada, Finland, Israel, Japan, Spain, Sweden, and Switzerland). Neonates of 24 and 28 weeks' gestational age who survived 7 days and who received PNS were included. We assessed temporal trend of rates of systemic PNS receipt and BPD/death. RESULTS: A total of 47,401 neonates were included. The mean (SD) gestational age was 26.4 (1.3) weeks and birth weight was 915 (238) g. The PNS receipt rate was 21% (12-28% across networks) and increased over the years (18% in 2010 to 26% in 2018; p < 0.01). The BPD rate was 39% (28-44% across networks) and remained unchanged over the years (35.2% in 2010 to 35.0% in 2018). Lower gestation, male sex, small for gestational age status, and presence of persistent ductus arteriosus (PDA) were associated with higher rates of PNS receipt, BPD, and BPD/death. CONCLUSION: The use of PNS in extremely preterm neonates increased, but there was no correlation between increased use and the BPD rate. Research is needed to determine the optimal timing, dose, and indication for PNS use in preterm neonates.

Preterm birth in the Nordic countries-Capacity, management and outcome in neonatal care.

AIM: Organisation of care, perinatal and neonatal management of very preterm infants in the Nordic regions were hypothesised to vary significantly. The aim of this observational study was to test this hypothesis. METHODS: Information on preterm infants in the 21 greater healthcare regions of Denmark, Finland, Iceland, Norway and Sweden was gathered from national registers in 2021. Preterm birth rates, case-mix, perinatal interventions, neonatal morbidity and survival to hospital discharge in very (<32 weeks) and extremely preterm infants (<28 weeks of gestational age) were compared. RESULTS: Out of 287 642 infants born alive, 16 567 (5.8%) were preterm, 2389 (0.83%) very preterm and 800 (0.28%) were extremely preterm. In very preterm infants, exposure to antenatal corticosteroids varied from 85% to 98%, live births occurring at regional centres from 48% to 100%, surfactant treatment from 28% to 69% and use of mechanical ventilation varied from 13% to 77% (p < 0.05 for all comparisons). Significant regional variations within and between countries were also seen in capacity in neonatal care, case-mix and number of admissions, whereas there were no statistically significant differences in survival or major neonatal morbidities. CONCLUSION: Management of very preterm infants exhibited significant regional variations in the Nordic countries.

Overlap between EEC and AEC syndrome and immunodeficiency in a preterm infant with a TP63 variant.

Pathogenic variants in the transcription factor TP63 gene cause a variety of clinical phenotypes, such as ectrodactyly-ectodermal dysplasia-clefting (EEC) syndrome and ankyloblepharon-ectodermal dysplasia-clefting (AEC) syndrome. Historically, TP63-related phenotypes have been divided into several syndromes based on both the clinical presentation and location of the pathogenic variant on the TP63 gene. This division is complicated by significant overlap between syndromes. Here we describe a patient with clinical characteristics of different TP63-associated syndromes (cleft lip and palate, split feet, ectropion, erosions of the skin and corneas), associated with a de novo heterozygous pathogenic variant c.1681 T>C, p.(Cys561Arg) in exon 13 of the TP63 gene. Our patient also developed enlargement of the left-sided cardiac compartments and secondary mitral insufficiency, which is a novel finding, and immune deficiency, which has only rarely been reported. The clinical course was further complicated by prematurity and very low birth weight. We illustrate the overlapping features of EEC and AEC syndrome and multidisciplinary care needed to address the various clinical challenges.

Detailed prenatal and postnatal MRI findings and clinical analysis of RAF1 in Noonan syndrome.

Noonan syndrome is a genetically heterogeneous developmental disorder, which usually includes findings such as short stature, facial dysmorphia, cardiac abnormalities and a varying degree of intellectual disability. We present a unique case of a rare variant of Noonan syndrome in a very preterm female infant born at 28 + 4 gestational weeks, with abnormal radiological findings visible at fetal magnetic resonance imaging (MRI) and evolution of the brain lesions during infancy.

International Variation in the Management of Patent Ductus Arteriosus and Its Association with Infant Outcomes: A Survey and Linked Cohort Study.

OBJECTIVE: To assess whether treating patients with a presymptomatic patent ductus arteriosus (PDA), based on early routine echocardiography, performed regardless of clinical signs, improved outcomes. STUDY DESIGN: This multicenter, survey-linked retrospective cohort study used an institutional-level questionnaire and individual patient-level data and included infants of <29 weeks of gestation born in 2014-2016 and admitted to tertiary neonatal intensive care units (NICUs) of 9 population-based national or regional neonatal networks. Infants in NICUs receiving treatment of presymptomatic PDA identified by routine echocardiography and those not were compared for the primary composite outcome (early death [≤7 days after birth] or severe intraventricular hemorrhage) and secondary outcomes (any in-hospital mortality and major morbidities). RESULTS: The unit survey (response rates of 86%) revealed a wide variation among networks in the treatment of presymptomatic PDA (7%-86%). Among 246 NICUs with 17 936 infants (mean gestational age of 26 weeks), 126 NICUs (51%) with 7785 infants treated presymptomatic PDA. The primary outcome of early death or severe intraventricular hemorrhage was not significantly different between the NICUs treating presymptomatic PDA and those who did not (17% vs 21%; aOR 1.00, 95% CI 0.85-1.18). The NICUs treating presymptomatic PDA had greater odds of retinopathy of prematurity treatment (13% vs 7%; aOR 1.47, 95% CI 1.01-2.12); however, it was not significant in a sensitivity analysis excluding Japanese data. CONCLUSIONS: Treating presymptomatic PDA detected by routine echocardiography was commonplace but associated with no significant benefits. Well-designed trials are needed to assess the efficacy and safety of early targeted PDA treatment.

Means of reaching successful antenatal transfers to level 3 hospitals in cases of threatened very preterm deliveries: a national survey.

INTRODUCTION: Centralization of very preterm deliveries to level 3 hospitals is recommended to improve infant survival and prevent brain injury. We studied the clinical practices of centralization from level 2 to level 3 hospitals in cases of threatening very preterm delivery in Finland. MATERIALS AND METHODS: Obstetricians in all 16 level 2 hospitals in Finland were invited to participate in an online survey regarding antenatal transfer to level 3 hospitals among women with threatened delivery below 32 gestational weeks. We report clinical thresholds used as indications and contraindications for antenatal transfers, and logistical factors related to transfers. RESULTS: Twelve out of 16 (75%) hospitals completed the survey. The lower gestational age threshold for antenatal transfer ranged from 22 + 0 to 23 + 0 weeks. All hospitals regarded preterm premature rupture of membranes, chorioamnionitis, and severe pre-eclampsia as indications for antenatal transfer to a level 3 hospital. Most hospitals reported transferring women in spite of regular contractions (interval over 5 min) or cervical dilatation up to 4 cm. Suspicion of placental abruption, abnormal cardiotocography tracing and poor maternal condition were the most frequently reported contraindications for antenatal transfer. The time to arrange antenatal transfer was less than 2 h in all hospitals, and overcrowding of level 3 hospitals rarely hindered antenatal transfer. CONCLUSIONS: Successful centralization of very preterm deliveries is reached in Finland by rapid and active antenatal transfers. This study identified clinical thresholds used by obstetricians in a setting of long distances and high centralization rate.

Five-minute Apgar score and outcomes in neonates of 24-28 weeks' gestation.

OBJECTIVES: To assess associations between 5 min Apgar score and mortality and severe neurological injury (SNI) and to report test characteristics in preterm neonates. DESIGN, SETTING AND PATIENTS: Retrospective cohort study of neonates 240 to 286 weeks' gestation born between 2007 and 2016 and admitted to neonatal units in 11 high-income countries. EXPOSURE: 5 min Apgar score. MAIN OUTCOME MEASURES: In-hospital mortality and SNI defined as grade 3 or 4 periventricular/intraventricular haemorrhage or periventricular leukomalacia. Outcome rates were calculated for each Apgar score and compared after adjustment. The diagnostic characteristics and ORs for each value from 0 versus 1-10 to 0-9 versus 10, with 1-point increments were calculated. RESULTS: Among 92 412 included neonates, as 5 min Apgar score increased from 0 to 10, mortality decreased from 60% to 8%. However, no clear increasing or decreasing pattern was identified for SNI. There was an increase in sensitivity and decrease in specificity for both mortality and SNI associated with increasing scores. The Apgar score alone had an area under the curve of 0.64 for predicting mortality, which increased to 0.73 with the addition of gestational age. CONCLUSIONS: In neonates of 24-28 weeks' gestation admitted to neonatal units, higher 5 min Apgar score was associated with lower mortality in a graded manner, while the association with SNI remained relatively constant at all scores. Among survivors, low Apgar scores did not predict SNI.

Variations in Neonatal Length of Stay of Babies Born Extremely Preterm: An International Comparison Between iNeo Networks.

OBJECTIVE: To compare length of stay (LOS) in neonatal care for babies born extremely preterm admitted to networks participating in the International Network for Evaluating Outcomes of Neonates (iNeo). STUDY DESIGN: Data were extracted for babies admitted from 2014 to 2016 and born at 24 to 28 weeks of gestational age (n = 28 204). Median LOS was calculated for each network for babies who survived and those who died while in neonatal care. A linear regression model was used to investigate differences in LOS between networks after adjusting for gestational age, birth weight z score, sex, and multiplicity. A sensitivity analysis was conducted for babies who were discharged home directly. RESULTS: Observed median LOS for babies who survived was longest in Japan (107 days); this result persisted after adjustment (20.7 days more than reference, 95% CI 19.3-22.1). Finland had the shortest adjusted LOS (-4.8 days less than reference, 95% CI -7.3 to -2.3). For each week's increase in gestational age at birth, LOS decreased by 12.1 days (95% CI -12.3 to -11.9). Multiplicity and male sex predicted mean increases in LOS of 2.6 (95% CI 2.0-3.2) and 2.1 (95% CI 1.6-2.6) days, respectively. CONCLUSIONS: We identified between-network differences in LOS of up to 3 weeks for babies born extremely preterm. Some of these may be partly explained by differences in mortality, but unexplained variations also may be related to differences in clinical care practices and healthcare systems between countries.

Family Rooms in Neonatal Intensive Care Units and Neonatal Outcomes: An International Survey and Linked Cohort Study.

OBJECTIVES: To evaluate the proportion of neonatal intensive care units with facilities supporting parental presence in their infants' rooms throughout the 24-hour day (ie, infant-parent rooms) in high-income countries and to analyze the association of this with outcomes of extremely preterm infants. STUDY DESIGN: In this survey and linked cohort study, we analyzed unit design and facilities for parents in 10 neonatal networks of 11 countries. We compared the composite outcome of mortality or major morbidity, length of stay, and individual morbidities between neonates admitted to units with and without infant-parent rooms by linking survey responses to patient data from 2015 for neonates of less than 29 weeks of gestation. RESULTS: Of 331 units, 13.3% (44/331) provided infant-parent rooms. Patient-level data were available for 4662 infants admitted to 159 units in 7 networks; 28% of the infants were cared for in units with infant-parent rooms. Neonates from units with infant-parent rooms had lower odds of mortality or major morbidity (aOR, 0.76; 95% CI, 0.64-0.89), including lower odds of sepsis and bronchopulmonary dysplasia, than those from units without infant-parent rooms. The adjusted mean length of stay was 3.4 days shorter (95%, CI -4.7 to -3.1) in the units with infant-parent rooms. CONCLUSIONS: The majority of units in high-income countries lack facilities to support parents' presence in their infants' rooms 24 hours per day. The availability vs absence of infant-parent rooms was associated with lower odds of composite outcome of mortality or major morbidity and a shorter length of stay.

Neonatal Intensive Care Unit-Level Patent Ductus Arteriosus Treatment Rates and Outcomes in Infants Born Extremely Preterm.

OBJECTIVES: To assess associations between neonatal intensive care unit (NICU)-level patent ductus arteriosus (PDA) treatment rates (pharmacologic or surgical) and neonatal outcomes. STUDY DESIGN: This cohort study included infants born at 24-28 weeks of gestation and birth weight <1500 g in 2007-2015 in NICUs caring for ≥100 eligible infants in 6 countries. The ratio of observed/expected (O/E) PDA treatment rates was derived for each NICU by estimating the expected rate using a logistic regression model adjusted for potential confounders and network. The primary composite outcome was death or severe neurologic injury (grades III-IV intraventricular hemorrhage or periventricular leukomalacia). The associations between the NICU-level O/E PDA treatment ratio and neonatal outcomes were assessed using linear regression analyses including a quadratic effect (a square term) of the O/E PDA treatment ratio. RESULTS: From 139 NICUs, 39 096 infants were included. The overall PDA treatment rate was 45% in the cohort (13%-77% by NICU) and the O/E PDA treatment ratio ranged from 0.30 to 2.14. The relationship between the O/E PDA treatment ratio and primary composite outcome was U-shaped, with the nadir at a ratio of 1.13 and a significant quadratic effect (P<.001). U-shaped relationships were also identified with death, severe neurologic injury, and necrotizing enterocolitis. CONCLUSIONS: Both low and high PDA treatment rates were associated with death or severe neurologic injury, whereas a moderate approach was associated with optimal outcomes.

Survey shows marked variations in approaches to redirection of care for critically ill very preterm infants in 11 countries.

AIM: We surveyed care practices for critically ill very preterm infants admitted to neonatal intensive care units (NICUs) in the International Network for Evaluating Outcomes in Neonates (iNeo) to identify differences relevant to outcome comparisons. METHODS: We conducted an online survey on care practices for critically ill very preterm infants and infants with severe intracranial haemorrhage (ICH). The survey was distributed in 2015 to representatives of 390 NICUs in 11 countries. Survey replies were compared with network incidence of death and severe ICH for infants born between 230/7 and 286/7  weeks of gestation from January 1, 2015, to December 31, 2015. RESULTS: Most units in Israel, Japan and Tuscany, Italy, favoured withholding care when care was considered futile, whereas most units in other networks favoured redirection of care. For infants with bilateral grade 4 ICH, redirection of care was very frequently (≥90% of cases) offered in the majority of units in Australia and New Zealand and Switzerland, but rarely in other networks. Networks where redirection of care was frequently offered for severe ICH had lower rates of survivors with severe ICH. CONCLUSION: We identified marked inter-network differences in care approaches that need to be considered when comparing outcomes.

Preventive strategies and factors associated with surgically treated necrotising enterocolitis in extremely preterm infants: an international unit survey linked with retrospective cohort data analysis.

OBJECTIVES: To compare necrotising enterocolitis (NEC) prevention practices and NEC associated factors between units from eight countries of the International Network for Evaluation of Outcomes of Neonates, and to assess their association with surgical NEC rates. DESIGN: Prospective unit-level survey combined with retrospective cohort study. SETTING: Neonatal intensive care units in Australia/New Zealand, Canada, Finland, Israel, Spain, Sweden, Switzerland and Tuscany (Italy). PATIENTS: Extremely preterm infants born between 240 to 286 weeks' gestation, with birth weights<1500 g, and admitted between 2014-2015. EXPOSURES: NEC prevention practices (probiotics, feeding, donor milk) using responses of an on-line pre-piloted questionnaire containing 10 questions and factors associated with NEC in literature (antenatal steroids, c-section, indomethacin treated patent ductus arteriosus and sepsis) using cohort data. OUTCOME MEASURES: Surgical NEC rates and death following NEC using cohort data. RESULTS: The survey response rate was 91% (153 units). Both probiotic provision and donor milk availability varied between 0%-100% among networks whereas feeding initiation and advancement rates were similar in most networks. The 9792 infants included in the cohort study to link survey results and cohort outcomes, revealed similar baseline characteristics but considerable differences in factors associated with NEC between networks. 397 (4.1%) neonates underwent NEC surgery, ranging from 2.4%-8.4% between networks. Standardised ratios for surgical NEC were lower for Australia/New Zealand, higher for Spain, and comparable for the remaining six networks. CONCLUSIONS: The variation in implementation of NEC prevention practices and in factors associated with NEC in literature could not be associated with the variation in surgical NEC incidence. This corroborates the current lack of consensus surrounding the use of preventive strategies for NEC and emphasises the need for research.

Unit-Level Variations in Healthcare Professionals' Availability for Preterm Neonates <29 Weeks' Gestation: An International Survey.

INTRODUCTION: The availability of and variability in healthcare professionals in neonatal units in different countries has not been well characterized. Our objective was to identify variations in the healthcare professionals for preterm neonates in 10 national or regional neonatal networks participating in the International Network for Evaluating Outcomes (iNeo) of neonates. METHOD: Online, pre-piloted questionnaires about the availability of healthcare professionals were sent to the directors of 390 tertiary neonatal units in 10 international networks: Australia/New Zealand, Canada, Finland, Illinois, Israel, Japan, Spain, Sweden, Switzerland, and Tuscany. RESULTS: Overall, 325 of 390 units (83%) responded. About half of the units (48%; 156/325) cared for 11-30 neonates/day and had team-based (43%; 138/325) care models. Neonatologists were present 24 h a day in 59% of the units (191/325), junior doctors in 60% (194/325), and nurse practitioners in 36% (116/325). A nurse-to-patient ratio of 1:1 for infants who are unstable and require complex care was used in 52% of the units (170/325), whereas a ratio of 1:1 or 1:2 for neonates requiring multisystem support was available in 59% (192/325) of the units. Availability of a respiratory therapist (15%, 49/325), pharmacist (40%, 130/325), dietitian (34%, 112/325), social worker (81%, 263/325), lactation consultant (45%, 146/325), parent buddy (6%, 19/325), or parents' resource personnel (11%, 34/325) were widely variable between units. CONCLUSIONS: We identified variability in the availability and organization of the healthcare professionals between and within countries for the care of extremely preterm neonates. Further research is needed to associate healthcare workers' availability and outcomes.

Association of early postnatal transfer and birth outside a tertiary hospital with mortality and severe brain injury in extremely preterm infants: observational cohort study with propensity score matching.

OBJECTIVE: To determine if postnatal transfer or birth in a non-tertiary hospital is associated with adverse outcomes. DESIGN: Observational cohort study with propensity score matching. SETTING: National health service neonatal care in England; population data held in the National Neonatal Research Database. PARTICIPANTS: Extremely preterm infants born at less than 28 gestational weeks between 2008 and 2015 (n=17 577) grouped based on birth hospital and transfer within 48 hours of birth: upward transfer (non-tertiary to tertiary hospital, n=2158), non-tertiary care (born in non-tertiary hospital; not transferred, n=2668), and controls (born in tertiary hospital; not transferred, n=10 866). Infants were matched on propensity scores and predefined background variables to form subgroups with near identical distributions of confounders. Infants transferred between tertiary hospitals (horizontal transfer) were separately matched to controls in a 1:5 ratio. MAIN OUTCOME MEASURES: Death, severe brain injury, and survival without severe brain injury. RESULTS: 2181 infants, 727 from each group (upward transfer, non-tertiary care, and control) were well matched. Compared with controls, infants in the upward transfer group had no significant difference in the odds of death before discharge (odds ratio 1.22, 95% confidence interval 0.92 to 1.61) but significantly higher odds of severe brain injury (2.32, 1.78 to 3.06; number needed to treat (NNT) 8) and significantly lower odds of survival without severe brain injury (0.60, 0.47 to 0.76; NNT 9). Compared with controls, infants in the non-tertiary care group had significantly higher odds of death (1.34, 1.02 to 1.77; NNT 20) but no significant difference in the odds of severe brain injury (0.95, 0.70 to 1.30) or survival without severe brain injury (0.82, 0.64 to 1.05). Compared with infants in the upward transfer group, infants in the non-tertiary care group had no significant difference in death before discharge (1.10, 0.84 to 1.44) but significantly lower odds of severe brain injury (0.41, 0.31 to 0.53; NNT 8) and significantly higher odds of survival without severe brain injury (1.37, 1.09 to 1.73; NNT 14). No significant differences were found in outcomes between the horizontal transfer group (n=305) and controls (n=1525). CONCLUSIONS: In extremely preterm infants, birth in a non-tertiary hospital and transfer within 48 hours are associated with poor outcomes when compared with birth in a tertiary setting. We recommend perinatal services promote pathways that facilitate delivery of extremely preterm infants in tertiary hospitals in preference to postnatal transfer.

The International Network for Evaluating Outcomes (iNeo) of neonates: evolution, progress and opportunities.

Neonates born very preterm (before 32 weeks' gestational age), are a significant public health concern because of their high-risk of mortality and life-long disability. In addition, caring for very preterm neonates can be expensive, both during their initial hospitalization and their long-term cost of permanent impairments. To address these issues, national and regional neonatal networks around the world collect and analyse data from their constituents to identify trends in outcomes, and conduct benchmarking, audit and research. Improving neonatal outcomes and reducing health care costs is a global problem that can be addressed using collaborative approaches to assess practice variation between countries, conduct research and implement evidence-based practices. The International Network for Evaluating Outcomes (iNeo) of neonates was established in 2013 with the goal of improving outcomes for very preterm neonates through international collaboration and comparisons. To date, 10 national or regional population-based neonatal networks/datasets participate in iNeo collaboration. The initiative now includes data on >200,000 very preterm neonates and has conducted important epidemiological studies evaluating outcomes, variations and trends. The collaboration has also surveyed >320 neonatal units worldwide to learn about variations in practices, healthcare service delivery, and physical, environmental and manpower related factors and support services for parents. The iNeo collaboration serves as a strong international platform for Neonatal-Perinatal health services research that facilitates international data sharing, capacity building, and global efforts to improve very preterm neonate care.

Trends in centralization of very preterm deliveries and neonatal survival in Finland in 1987-2017.

Very preterm infants are at high risk of death and complications of prematurity. Optimal outcomes are achieved if these infants are delivered in hospitals with the highest level of neonatal expertise. Centralization of very preterm deliveries to such hospitals has been recommended for decades, and is supported by a large body of literature. However, centralization may not be easy to implement due to financial, organizational and workforce-related issues. In this review, we present the scientific background for centralization, how it has been successfully implemented in Finland and how neonatal survival has changed following this implementation.

Neonatal Outcomes of Very Preterm or Very Low Birth Weight Triplets.

OBJECTIVES: To compare the neonatal outcomes of very preterm triplets with those of matched singletons using a large international cohort. METHODS: A retrospective matched-cohort study of preterm triplets and singletons born between 2007 and 2013 in the International Network for Evaluation of Outcomes in neonates database countries and matched by gestational age, sex, and country of birth was conducted. The primary outcome was a composite of mortality or severe neonatal morbidity (severe neurologic injury, treated retinopathy of prematurity, and bronchopulmonary dysplasia). Unadjusted and adjusted odds ratios with 95% confidence intervals (CIs) were calculated for model 1 (maternal hypertension and birth weight z score) and model 2 (variables in model 1, antenatal steroids, and mode of birth). Models were fitted with generalizing estimating equations and random effects modeling to account for clustering. RESULTS: A total of 6079 triplets of 24 to 32 weeks' gestation or 500 to 1499 g birth weight and 18 232 matched singletons were included. There was no difference in the primary outcome between triplets and singletons (23.4% vs 24.0%, adjusted odds ratio: 0.91, 95% CI: 0.83-1.01 for model 1 and 1.00, 95% CI: 0.90-1.11 for model 2). Rates of severe neonatal morbidities did not differ significantly between triplets and singletons. The results were also similar for a subsample of the cohort (1648 triplets and 4944 matched singletons) born at 24 to 28 weeks' gestation. CONCLUSIONS: No significant differences were identified in mortality or major neonatal morbidities between triplets who were very low birth weight or very preterm and matched singletons.

Variations in Oxygen Saturation Targeting, and Retinopathy of Prematurity Screening and Treatment Criteria in Neonatal Intensive Care Units: An International Survey.

BACKGROUND: Rates of retinopathy of prematurity (ROP) and ROP treatment vary between neonatal intensive care units (NICUs). Neonatal care practices, including oxygen saturation (SpO2) targets and criteria for the screening and treatment of ROP, are potential contributing factors to the variations. OBJECTIVES: To survey variations in SpO2 targets in 2015 (and whether there had been recent changes) and criteria for ROP screening and treatment across the networks of the International Network for Evaluating Outcomes in Neonates (iNeo). METHODS: Online prepiloted questionnaires on treatment practices for preterm infants were sent to the directors of 390 NICUs in 10 collaborating iNeo networks. Nine questions were asked and the results were summarized and compared. RESULTS: Overall, 329/390 (84%) NICUs responded, and a majority (60%) recently made changes in upper and lower SpO2 target limits, with the median set higher than previously by 2-3% in 8 of 10 networks. After the changes, fewer NICUs (15 vs. 28%) set an upper SpO2 target limit > 95% and fewer (3 vs. 5%) a lower limit < 85%. There were variations in ROP screening criteria, and only in the Swedish network did all NICUs follow a single guideline. The initial retinal examination was carried out by an ophthalmologist in all but 6 NICUs, and retinal photography was used in 20% but most commonly as an adjunct to indirect ophthalmoscopy. CONCLUSIONS: There is considerable variation in SpO2 targets and ROP screening and treatment criteria, both within networks and between countries.